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APPLICATIONS OF BIOTECHNOLOGY: PANACEA or PANDORA'S BOX?
GENETIC ENGINEERING OF AGRICULTURAL SPECIES
Foreign genes are under study for insertion into commercial plant species to
confer...
selective herbicide resistance
herbivore resistance
increased yield
improved nutrient balance
plant-grown vaccines and pharmaceuticals
insert your Brave New Idea here
Problems? You bet!
possible allergic reactions in humans to foreign proteins
increased use of herbicides --> increased human exposure
jumping of plasmids from commercial crops to "weed" species resulting
in- herbicide-resistant weeds
- toxicity to commercially important pollinators and their larvae
- eco-mayhem not yet predicted
And it doesn't stop with plants, of course. Transgenic animals are
becoming practically commonplace.
transfection accomplished at zygote
stage (affects all future
generations)
transfection accomplished in target cells (affects only the
individual; not future generations)
This dichotomy is at the root of the future of human gene therapy. If we
alter human disease genes, do we plan to do it at the zygote stage--or the
somatic stage? Huge bioethical implications!
GENE THERAPY
The idea is simple; the practice is not. Using the sequencing, cloning
and vector-insertion techniques we've discussed, scientists hope to be able
to deliver working versions of genes to individuals who were born with
deleterious mutant versions of the gene.
As you might guess from the low success rates of vector transfection, this
is a dicey procedure, and the techniques are still crude, at best.
Still, technologies are improving at an exponential rate, and it is true
that some devastating genetic diseases might some day be cured by the
insertion of wild type genes to replace the faulty, non-functional ones.
Germ Line Therapy - this is the transfection of germ cells with "desired"
genes, and it does have evolutionary consequences. Not only is a person
carrying a deleterious allele cured, but some of his/her gametes might also
be "cured"--meaning the end to the heritability of the particular disorder
by that individual's offspring.
Problem: transfection fragments often insert haphazardly (ectopically,
i.e., not in its usual locus) which means not
only that normal gene function could be disrupted if the insertion takes
place in the middle of a normal gene, but also that even if the normal gene
inserts in a non-disruptive spot, it has not replaced the disease gene.
It can still be passed on to progeny, even if the parental organism is
functional.
Somatic Gene Therapy - This targets only the affected body cells, and
has no evolutionary consequences. Only some somatic cells are
transfected--enough to effect a cure or confer effective function. (Note
that unless one transfects a one-celled embryo, gene therapy cannot
correct genetic errors in every cell of the body. Hence, this type of
therapy is useful only for disorders that are highly tissue-specific and
treatable if SOME functional cells are present. Diabetes is one such
disorder, as functional Islet of Langerhans cells can be created
transgenically so that the individual can produce insulin in some cells,
even if many of his/her other cells are not functional.
The difference between these two types of therapy is illustrated HERE.
PRENATAL GENETIC TESTING
Recombinant DNA probes can be used in tissue cultures obtained via
amniocentesis
or chorionic villus sampling to detect
genetic abnormalities in human (or other species) fetuses.
Usually,
detection of disorders is done via expression of normal protein products
present or not present in the cultured cells.
Recombinant DNA could be used for greater accuracy, since cloned
probes of the normal gene could be used to detect abnormalities at the
level of the DNA.
Example: Sickle cell fetuses, because of the GAG-to-GTG mutation
resulting in the disorder, also disrupt a restriction site normally present
in normal fetuses. Detection of the lack of this restriction site could
be useful in prenatal diagnosis of Sickle Cell.
Once the human genome project reveals normal sequences for various
genes, altered sequences will be detectable via oligonucleotide probes
specific to the gene of interest.
AMPLIFICATION OF INTERESTING, BUT MYSTERIOUS DNA
There are also sequences with no known function...
- HIGHLY REPETITIVE CENTROMERIC DNA - tandem repeats in the
(untranscribed)
heterochromatin flanking the centromeres are there, but we don't yet know
why.
- VNTRs - Variable Number Tandem Repeats are 1-5 kb long, and consist
of variable numbers of adjacent repeats. No one knows what they do, but
they are *highly* variable among individuals. These are the fragments of
DNA that are used as DNA FINGERPRINTS,
and are used extensively in criminal forensics.
(PCR is used to amplify the fragments into a usable sample).
Again, once these are labeled with radioactive probe, a useful picture of
the gel can be made.
- TRANSPOSED SEQUENCES - Multiple copies of small DNA segments called
TRANSPOSABLE GENETIC ELEMENTS exist throughout the genome, and some can
excise and move to other parts of the genome. Their function is not
known, and some suspect that they could be remnants of "parasitic" or
"selfish" DNA
that simply goes along for the ride without regard for the host.
- RETROTRANSPOSONS are similar, but have been reverse transcribed from RNA
into DNA which then inserts into the host genome. These little buggers
act a bit like retroviruses.
- SPACER DNA - Is just what it sounds like. Probably spaces between
genes, possibly selfish DNA that no longer moves about. We just don't
know yet. Life isn't always fair.
